Isothermal titration calorimetry (ITC) is a powerful method for determining the thermodynamic contributions of enthalpy (ΔH) and entropy changes (ΔS) on protein-ligand binding. This unique feature of ITC, coupled to advancements in instrumentation, has led to its emerging use in drug discovery. The thermodynamic profiles of the interaction between target protein and potential drug compounds provide effective guidelines for lead selection and optimization. In this review, we describe an example of ITC analysis of a drug target protein, PPARγ and summarize recent trends in the use of ITC as a tool for rational drug design.

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The number of therapeutic antibody under development has increased markedly over the last several years and this trend continues. In fact, there are more than 20 approved antibodies on the US market. One of the most important characteristics of the antibodies for the successful development as biotherapeutics is their conformational stability, which can be defined as the ability of molecule to maintain the native higher-order structure under broad range of conditions. The antibodies in unfolded state frequently have greater propensity to form aggregates than those in native state. The differential scanning calorimetry (DSC) is the only technique for direct measurement of the thermodynamic parameters accompanied by the thermal unfolding. The DSC is also an effective tool to estimate the contribution of each domain to overall stability for multi-domain protein such as antibodies. Although thermal stabilities of different antibodies have been examined by using DSC, apparent unfolding temperature where heat capacity takes maximum value was mainly discussed and thermodynamic parameters of each domain and inter-domain interactions were not estimated. It is now expected to establish analytical technique that takes intrinsic stabilities of each domain and inter-domain interactions into account for complete understanding of thermodynamics of whole antibody.

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Multicomponent crystals which contain API (active pharmaceutical ingredients) molecule are called as pharmaceutical cocrystals. Although there is currently some controversy regarding the classification and terminology for crystals consisting of more than one component, these systems are typically classified into salts, solvates (including hydrates) and cocrystals. Recently, the formation of cocrystal is attractive technique for improving the physicochemical properties of API. In this short review, screening and characterization of pharmaceutical cocrystals by using thermal analysis are introduced with advantages of cocrystallization in the development of solid dosage forms. In addition, preparing method of cocrystals for production scale by hotmelt extrusion technology is also described.

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Solid dispersion is recognized as promising formulation technology to improve solubility and bioavailability of poorly soluble compounds. However, its practical application for commercial products is still challenging because of its physical/chemical instability. It is very important to know why polymers in solid dispersions stabilize amorphous compounds for coping with challenges. Although stabilization mechamisms of polymer in solid dispersions have been reported, their details are still need to be investigated. In this review, the study results investigating the effets of polymers in solid dispersions agaist crystallization are introduced to establish theoretical rationale for selecting appropriate carriers of solid dispersions in formulation development of pharmaceutical products.

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